Fillers can be used in soft tissue augmentation to aesthetically reduce the effects of aging and other soft tissue defects. For example, it is desirable for a filler that is to be used intradermally to be absorbable and soft to the touch. In this case, the filler should not be palpable under the skin either initially upon application or over time. Absorbable polymers that are known to be soft to the touch are those having low glass transition temperatures, including but not limited to ε-caprolactone and p-dioxanone, and copolymers thereof.
A filler is ideally easy to use and produces reproducible and long-lasting results. For example, it may be desirable for the filler to be comprised of microspheres that can pass through a small needle for injection subcutaneously or intradermally, without aggregating or agglomerating under pressure, thereby avoiding clogging of a delivery device such as a needle. Further, if microspheres are utilized, it is desirable for the microspheres to retain their distinct spherical shape without aggregating or agglomerating (hereinafter referred to as “dimensional stability”), upon manufacture, storage and physical transport. Finally, in some situations it may be desirable for these microspheres to retain their distinct spherical shape after implantation, to avoid agglomeration of the microspheres subcutaneously or interdermally, which would produce an unnatural appearance in the skin.
U.S. Pat. No. 6,716,251 describes absorbable microspheres or microparticles suspended in a gel, where the microspheres or microparticles may be polycaprolactones, polylactides, polyglycolides and their copolymers. Although this reference suggests the use of copolymers of polycaprolactones, polylactides, and polyglycolides, preferred polymers are poly-L-lactic acid, poly-D-lactic acid, or a mixture thereof, having a molecular mass ranging from between 70,000 and 175,000 Dalton, and preferably between 120,000 and 170,000 Dalton.
It is possible to achieve the aforementioned combination of properties, i.e., “softness” and dimensional stability, for example, by utilizing copolymers to make microspheres having a low glass transition temperature and sufficient crystallinity to maintain their dimensional stability. Although it is believed that the polylactide microspheres exemplified in U.S. Pat. No. 6,716,251 would have sufficient crystallinity to be dimensionally stable since poly-L-lactides and poly-D-lactides are known to be highly crystalline, one would expect the microspheres to be hard and palpable under the skin, if injected subcutaneously or intradermally, since the glass transition temperature of poly-L-lactide and poly-D-lactide range from 56-65° C.
Therefore, it is desirable to achieve the aforementioned combination of properties of softness and dimensional stability, for example, by utilizing copolymers of ε-caprolactone or p-dioxanone to make microspheres having sufficient crystallinity to maintain their distinct spherical shape during manufacture, storage, transportation and use. Additionally, it is desirable to utilize copolymers of ε-caprolactone or p-dioxanone of specific molecular weights to make microspheres that can be absorbed in the human body within 6 to 24 months after implantation.
More specifically, it is desirable to utilize absorbable copolymers of ε-caprolactone or p-dioxanone that are semicrystalline in nature, to make microspheres that may be used, for example, in plastic surgery applications and that retain their distinct spherical shape upon manufacture, storage, and physical transportation.